Thorlacius S, Struewing J P, Hartge P, Olafsdottir G H, Sigvaldason H, Tryggvadottir L, Wacholder S, Tulinius H, Eyfjörd J E
Molecular and Cell Biology Research Laboratory, Icelandic Cancer Society, Reykjavik.
Lancet. 1998 Oct 24;352(9137):1337-9. doi: 10.1016/s0140-6736(98)03300-5.
Estimates of an 80-90% risk of breast cancer for carriers of germline mutations in the BRCA1 and BRCA2 genes are based on studies of families at high risk of breast cancer. Risk estimates for a population are possible if the mutation status of a representative sample of that population can be assessed. In Iceland, one common founder BRCA2 mutation occurs in 0.6% of the population. Iceland has a population-based cancer registry and a large collection of pedigrees, and estimation of cancer risk in mutation carriers is therefore possible.
We studied 575 breast-cancer patients, 541 women and 34 men unselected for family history of breast cancer. Data on cancer in first-degree relatives were available from the cancer registry. Risk of cancer was estimated by comparing the history of cancer in first-degree relatives of carriers and non-carriers.
56 (10.4%) of the 541 women and 13 (38%) of the 34 men carried the 999del5 mutation. The estimated risk of breast cancer at age 50 for all female carriers of the 999del5 mutation was 17.0% (95% CI 9.1-25.9) and 37.2% (22.4-53.9) at age 70.
The results of our population-based study show that the mean risk of breast cancer in carriers of mutation in BRCA2 is lower than previously suggested. Individual risk assessment will, however, have to take account of family history.
BRCA1和BRCA2基因种系突变携带者患乳腺癌的风险估计为80% - 90%，这是基于对乳腺癌高危家族的研究得出的。如果能够评估该人群代表性样本的突变状态，就有可能对人群的风险进行估计。在冰岛，一种常见的始祖BRCA2突变存在于0.6%的人群中。冰岛有基于人群的癌症登记处和大量的家系收集，因此有可能估计突变携带者的癌症风险。
我们研究了575例乳腺癌患者，541名女性和34名男性，这些患者未根据乳腺癌家族史进行选择。一级亲属的癌症数据可从癌症登记处获得。通过比较携带者和非携带者一级亲属的癌症病史来估计癌症风险。
541名女性中有56名（10.4%）和34名男性中有13名（38%）携带999del5突变。所有999del5突变女性携带者在50岁时患乳腺癌的估计风险为17.0%（95%置信区间9.1 - 25.9），在70岁时为37.2%（22.4 - 53.9）。
我们基于人群的研究结果表明，BRCA2突变携带者患乳腺癌的平均风险低于先前的推测。然而，个体风险评估必须考虑家族史。
